Bony tissues are connective tissues consisting of bone cells and extracellular matrices, but are different from other connective tissues in that the ossified connective substances within the extracellular matrices are inorganic. The inorganic substance consists mainly of calcium phosphate which exists as hydroxyapatite crystals (Ca10(PO4)(OH)2).
Bony tissues are hard enough to support and defend against physical stresses of the body, and their fracture or their density reduction or damage attributed to pathogenic changes may cause the body to suffer from deformity. When damaged or removed owing to any reasons, a bone has to be regenerated naturally or needs to be substituted with a prosthesis or a bone material from another body part by surgery. In addition, healing a physically broken (fractured) bone or a surgically damaged bone requires using various prosthetic tools, including artificial bones, for artificially relaying and immobilizing the bone. In this case, however, it takes a significantly long period of time for the bone to recover to its original figure and function while the patient suffers from serious physical and mental stresses. Further, as the healing procedure becomes long, the damaged part is increasingly apt to be under the danger of infection with germs, so that a perfect remedy may not be expected.
It remains an urgent need to develop methods for facilitating the medical treatment process (regeneration) of damaged bony tissues or inducing the morphogenesis of new bony tissues, or materials suitable for such treatment process. In connection, various selective materials such as bioceramics, composite materials and bone derivatives, as well as artificial fillers for bone recovery, such as natural or synthetic polymers have been developed.
Substitution of damaged bony tissues is also being undertaken by facilitating osteogenesis with various bone onlays and bone graft substitutes. Application of bone onlays and bone graft substitutes is conducted largely by two methods: an autograft method and an allograft method. Both of the two methods utilize human's bones to induce osteogenesis. The bones to be grafted must be similar in elastic modulus to bones adjacent to the graft area because graft materials greatly different in elastic modulus, e.g., metal grafts generate excess stresses.
However, grafting methods utilizing bone onlays also suffer from several problems. When adopting an autograft method, the grafts to be available are quantitatively limited. In addition, while a surgical operation is conducted to extirpate a required bone for autograft, it may be in danger of bacterial infection and loss of blood all at times. In addition, the areas wherefrom grafts are extirpated become poor in structural stability. The grafting technique, including the surgery operation, may force some patients to endure pain for a longer period of time than does fusion surgery. The allograft method has an advantage over the autograft method in that supply of allografts can be relatively achieved because they are obtained from allo-donators, but allogenic bones are far inferior in osteoinductive potential to autogenous bones and thus, can be used as only temporary supports.
Additional problems are also found in both the autograft and the allograft methods. For instance, since the grafts alone, used in the above graft methods, cannot offer stability enough to endure the spinal marrow, an internal fixing method needs to be conducted concurrently. In this case, metal fixing means are used, requiring a more complicated surgical operation. In addition, the operator must repeatedly trim the graft into a precise size to fit into a targeted bony tissue, which results in extending the time it takes for the surgical operation. Further, in general, a smooth surface of a graft cannot provide a frictional force necessary for the graft to fix between adjacent bony tissues. Thus, the trimming may be in danger of slipping of the trimmed graft from the bony tissues, breaking the structure of the grafted bony tissue and causing damage to the nerve system and the vascular system near the bony tissue.
In order to meet the necessity of safer and more convenient bone grafts, keen interest has recently been taken in bone graft substitutes, such as bioceramics. Calcium phosphate ceramics, one of the bioceramics, exhibit superior biocompatibility and are significantly free from the bacterial infection and immunological danger which may be caused upon allograft. Moreover, with the above advantages of allografting-bone grafts, calcium phosphate ceramics can be produced in abundance. In addition, such bioceramics are not only osteoconductive, but provide porous matrices which facilitate bone morphogenesis in bony tissues. However, bioceramics are disadvantageous in that internal fixation is required before grafting because their strength is too low to support the weight of the spinal marrow.
Development was also achieved on various compositions of medical cements which can be applied in vivo. Among them, healing cements consisting of calcium phosphate possess excellent flexibility because tetracalcium phosphate, a main constituent of calcium phosphate, can be transformed into hydroxyapatite during the healing process. However, the prolonged time period that it takes for these healing cements to cure makes it difficult to apply them in practice. Also, it is difficult to apply the healing cements in tissues where body fluid is abundant, because when the cements are brought into contacting with pseudo-body fluid immediately after forming a kneaded plaster by mixing the cements, the fluid may penetrate into and finally destroy the kneaded plaster.
If damaged, various body joints, such as the total hip joint, the total knee joint and the total shoulder joint, may be substituted by artificial bones. Available for this purpose are synthetic materials which are prepared from a mixture of polymethylmetachlorite (PMMA) and benzoilperoxide. The artificial bones prepared from the synthetic materials, however, suffer from the serious problem of being not degraded naturally in vivo. Therefore, newly growing bones are obstructed by the persistent artificial bones, so that a high fever occurs, hurting the neighboring tissues. Conventionally, a patient suffering from a hernia of the cervical spine, lumbar spine, or thoracic spine discs undergoes a surgical operation by use of autografts. To secure his or her own iliac bone, an additional operation must be performed on the patient, which forces him or her to suffer from additional pain and the patient may develop complications. Alternatively, bones taken from corpses, such as the fibula and ilium, are used as substitutes for use in the operation. This allografting operation certainly imposes a physically lighter burden on the patient, but suffers from many disadvantages of more feasible viral infection, poorer strength maintenance of grafts, higher material cost, and poorer biocompatibility. In addition, when allograft providers do not secure sufficient corpses, the supply and demand of allografts is not balanced. Further, allografts find difficulty in keeping bone strength suitable for the patients who suffer from osteoporosis or who undergo an operation on ossa faciei or tops of the odontoid process. Upon allograft, a loosening is apt to happen.
To surmount these defects of bone graft substitutes and manufacturing process of the existing goods and characteristics thereof, these inventors of the present invention have developed novel bone graft materials using animal bone.